Research Description
Insulin is a hormone produced by only one cell type in our body, the beta cell. Insulin is important for cells to be able to take up glucose, the main energy source of the body. However, in type 1 diabetes (T1D) the beta cells are destroyed, so no insulin is being produced. Consequently, glucose cannot enter the cells and accumulates in the blood. Patients with T1D need to inject insulin to lower blood glucose levels. But insulin administration is challenging. If too much insulin is injected, blood glucose levels can drop dangerously low. The first and most important defense against this drop is glucagon secretion from alpha cells, the beta cells’ neighbors. Glucagon opposes the effects of insulin by activating the production and release of glucose into the blood stream. Alpha and beta cells are neighbors for a reason: they communicate. Signals between the two cell types tell them when to start and stop working. If the beta cell secretes insulin, the alpha cell is silent and the other way around. If the beta cell is destroyed in T1D, the alpha cell is left without the beta cell signals and starts working around the clock rising blood glucose levels even more. However, when blood glucose levels drop and alpha cell action is needed, they are too exhausted to respond appropriately. Our aim is to reactivate these signals and test if that can rescue the alpha cell’s ability to respond to low glucose levels in T1D, allowing more effective diabetes therapy.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?My research is focused on preventing hypoglycemia, a serious complication for individuals with type 1 diabetes. Hypoglycemia occurs when blood glucose levels drop below optimal range. Increased glucagon secretion from the pancreatic alpha cell is the first and most important defense against hypoglycemia. Glucagon is a hormone that signals the liver to release glucose into the bloodstream and thus increase blood sugar levels. In type 1 diabetes this defensive mechanism is lost, not because the cells are gone, but because they are not responding appropriately. My project is focused on understanding the pathophysiological mechanisms that make alpha cells unresponsive to a drop in glucose levels during disease progression. If we can identify the underlying problem, we can manipulate the cells pharmacologically to restore alpha cell function and thus improve the management of diabetes and limit the risk of life-threatening hypoglycemic episodes.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?My project will not cure diabetes or take away the burden of living with the disease, but we might be able to make the treatment safer, reduce the risk of hypoglycemic episodes and thus give a little peace of mind. My Aim is to understand the underlying mechanism of alpha cell failure to counteract life-threatening hypoglycemia. Only if we understand the problem, we have a target to develop new therapeutic approaches and allow improved therapy of type 1 diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?I will always remember the moment I decided to become involved in diabetes research. As a student I was listening to a keynote lecture, when a mother described her daily struggle and fear as her daughter was diagnosed with type 1 diabetes. The fact that parents sleep next to their kids in fear of hypoglycemic episodes during the night was petrifying and eye opening to me. Since then, I specialized in diabetes research with a focus on islet physiology during disease progression. My long-term career goal is to become an independent investigator and to lead an academic research lab. This award will allow me to develop new technical skills, enhance my critical thinking, and become proficient in a research field to successfully transition to the next stage of my scientific career.
In what direction do you see the future of diabetes research going?In my eyes the best device to control glucose homeostasis are the cells that are naturally made for this job – the pancreatic islet cells. We have made tremendous breakthroughs in terms of stem cell development into beta like cells. The key challenge is now to translate scientific findings into effective therapies. As a physiologist I think that understanding human islet development and function will help scientist to design therapies and devices to not only improve survival and function of transplanted islet cells, but also restore signaling pathways to recover function of endogenous cells.